Electrical Field and Temperature Model of Nonthermal Irreversible Electroporation in Heterogeneous Tissues

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Charlotte Daniels ◽  
Boris Rubinsky
Keyword(s):  
Blood Vessels ◽  
Irreversible Electroporation ◽  
Surrounding Tissue ◽  
Electrical Field ◽  
Irreversible Damage ◽  
Minimally Invasive Surgical ◽  
Dimensional Finite Element ◽  
Nonthermal Irreversible Electroporation ◽  
Molecular Surgery ◽  
Heterogeneous Tissues

Nonthermal irreversible electroporation (NTIRE) is a new minimally invasive surgical technique that is part of the emerging field of molecular surgery, which holds the potential to treat diseases with unprecedented accuracy. NTIRE utilizes electrical pulses delivered to a targeted area, producing irreversible damage to the cell membrane. Because NTIRE does not cause thermal damage, the integrity of all other molecules, collagen, and elastin in the targeted area is preserved. Previous theoretical studies have only examined NTIRE in homogeneous tissues; however, biological structures are complex collections of diverse tissues. In order to develop electroporation as a precise treatment in clinical applications, realistic models are necessary. Therefore, the purpose of this study was to refine electroporation as a treatment by examining the effect of NTIRE in heterogeneous tissues of the prostate and breast. This study uses a two-dimensional finite element solution of the Laplace and bioheat equations to examine the effects of heterogeneities on electric field and temperature distribution. Three different heterogeneous structures were taken into account: nerves, blood vessels, and ducts. The results of this study demonstrate that heterogeneities significantly impact both the temperature and electrical field distribution in surrounding tissues, indicating that heterogeneities should not be neglected. The results were promising. While the surrounding tissue experienced a high electrical field, the axon of the nerve, the interior of the blood vessel, and the ducts experienced no electrical field. This indicates that blood vessels, nerves, and lactiferous ducts adjacent to a tumor treated with electroporation will survive, while the cancerous lesion is ablated. This study clearly demonstrates the importance of considering heterogeneity in NTIRE applications.

Irreversible Electroporation: An In Vivo Study Within the Dorsal Skin Fold Chamber

2011 ◽  
Author(s):  
Zhenpeng Qin ◽  
Jing Jiang ◽  
Gary Long ◽  
John C. Bischof
Keyword(s):  
Protein Denaturation ◽  
Irreversible Electroporation ◽  
Molecular Transport ◽  
Electrical Field ◽  
Irreversible Damage ◽  
Skin Fold ◽  
Electrical Pulses ◽  
Dorsal Skin Fold Chamber ◽  
Fast Procedure

Electroporation has been traditionally used to enhance molecular transport into cells (e.g. gene therapy) and through tissues (e.g. skin) by creating reversible pores with short electrical pulses [1]. Increasing the parameters (electrical field, pulse duration and number) can induce irreversible damage to the cells and tissue. Recently, irreversible electroporation (IRE) has been investigated as a new tumor ablation method [2]. The advantages of the IRE include the simple and fast procedure (train of μs pulses), sharp demarcation between treated and untreated regions, destruction of tumor cells while preserving the connective tissue, and minimal effect of immune response on treatment efficacy [3]. The unique interaction of electrical field with heterogeneous structures prevents damage to nerves, blood vessels and ducts [4]. IRE has been claimed to produce negligible thermal injury and protein denaturation typical to thermal ablation [5]. However, how each electroporation parameter in IRE affects tumor destruction and the possibility of heating remains to be studied in tumors vivo.

Nonthermal Irreversible Electroporation for Tissue Decellularization

2010 ◽  
Vol 132 (9) ◽  
Author(s):  
Mary Phillips ◽  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Electrical Parameters ◽  
Irreversible Damage ◽  
Tissue Scaffold ◽  
Electrical Fields ◽  
Nonthermal Irreversible Electroporation ◽  
Tissue Scaffolding ◽  
Living Tissues

Tissue scaffolding is a key component for tissue engineering, and the extracellular matrix (ECM) is nature’s ideal scaffold material. A conceptually different method is reported here for producing tissue scaffolds by decellularization of living tissues using nonthermal irreversible electroporation (NTIRE) pulsed electrical fields to cause nanoscale irreversible damage to the cell membrane in the targeted tissue while sparing the ECM and utilizing the body’s host response for decellularization. This study demonstrates that the method preserves the native tissue ECM and produces a scaffold that is functional and facilitates recellularization. A two-dimensional transient finite element solution of the Laplace and heat conduction equations was used to ensure that the electrical parameters used would not cause any thermal damage to the tissue scaffold. By performing NTIRE in vivo on the carotid artery, it is shown that in 3 days post NTIRE the immune system decellularizes the irreversible electroporated tissue and leaves behind a functional scaffold. In 7 days, there is evidence of endothelial regrowth, indicating that the artery scaffold maintained its function throughout the procedure and normal recellularization is taking place.

Some quantitative applications of vascular corrosion casting

1992 ◽  
Vol 50 (1) ◽  
pp. 738-739
Author(s):  
Fred E. Hossler
Keyword(s):  
Blood Vessels ◽  
Nuclear Orientation ◽  
Three Dimensional ◽  
Surrounding Tissue ◽  
Confocal Laser ◽  
Corrosion Casting ◽  
Venous Valve ◽  
Casting Technique ◽  
Low Viscosity ◽  
Quantitative Measurements

Preparation of replicas of the complex arrangement of blood vessels in various organs and tissues has been accomplished by infusing low viscosity resins into the vasculature. Subsequent removal of the surrounding tissue by maceration leaves a model of the intricate three-dimensional anatomy of the blood vessels of the tissue not obtainable by any other procedure. When applied with care, the vascular corrosion casting technique can reveal fine details of the microvasculature including endothelial nuclear orientation and distribution (Fig. 1), locations of arteriolar sphincters (Fig. 2), venous valve anatomy (Fig. 3), and vessel size, density, and branching patterns. Because casts faithfully replicate tissue vasculature, they can be used for quantitative measurements of that vasculature. The purpose of this report is to summarize and highlight some quantitative applications of vascular corrosion casting. In each example, casts were prepared by infusing Mercox, a methyl-methacrylate resin, and macerating the tissue with 20% KOH. Casts were either mounted for conventional scanning electron microscopy, or sliced for viewing with a confocal laser microscope.

scholarly journals Time-dependent impact of irreversible electroporation on pancreas, liver, blood vessels and nerves: a systematic review of experimental studies.

HPB ◽  
2019 ◽  
Vol 21 ◽  
pp. S541
Author(s):  
J.A. Vogel ◽  
E. van Veldhuisen ◽  
P.A. Agnass ◽  
J. Crezee ◽  
F. Dijk ◽  
...  
Keyword(s):  
Systematic Review ◽  
Blood Vessels ◽  
Irreversible Electroporation ◽  
Experimental Studies ◽  
Time Dependent

scholarly journals A Study on Nonthermal Irreversible Electroporation of the Thyroid

2019 ◽  
Vol 18 ◽  
pp. 153303381987630
Author(s):  
Yanpeng Lv ◽  
Yanfang Zhang ◽  
Jianwei Huang ◽  
Yunlong Wang ◽  
Boris Rubinsky
Keyword(s):  
Electric Fields ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Pulse Sequences ◽  
Cell Swelling ◽  
Tissue Type ◽  
Heterogeneous Structure ◽  
Treatment Protocols ◽  
Thyroid Ablation ◽  
Nonthermal Irreversible Electroporation

Background: Nonthermal irreversible electroporation is a minimally invasive surgery technology that employs high and brief electric fields to ablate undesirable tissues. Nonthermal irreversible electroporation can ablate only cells while preserving intact functional properties of the extracellular structures. Therefore, nonthermal irreversible electroporation can be used to ablate tissues safely near large blood vessels, the esophagus, or nerves. This suggests that it could be used for thyroid ablation abutting the esophagus. This study examines the feasibility of using nonthermal irreversible electroporation for thyroid ablation. Methods: Rats were used to evaluate the effects of nonthermal irreversible electroporation on the thyroid. The procedure entails the delivery of high electric field pulses (1-3 kV/cm, 100 microseconds) between 2 surface electrodes bracing the thyroid. The right lobe was treated with various nonthermal irreversible electroporation pulse sequences, and the left was the control. After 24 hours of the nonthermal irreversible electroporation treatment, the thyroid was examined with hemotoxylin and eosin histological analysis. Mathematical models of electric fields and the Joule heating-induced temperature raise in the thyroid were developed to examine the experimental results. Results: Treatment with nonthermal irreversible electroporation leads to follicular cells damage, associated with cell swelling, inflammatory cell infiltration, and cell ablation. Nonthermal irreversible electroporation spares the trachea structure. Unusually high electric fields, for these types of tissue, 3000 V/cm, are needed for thyroid ablation. The mathematical model suggests that this may be related to the heterogeneous structure of the thyroid-induced distortion of local electric fields. Moreover, most of the tissue does not experience thermal damage inducing temperature elevation. However, the heterogeneous structure of the thyroid may cause local hot spots with the potential for local thermal damage. Conclusion: Nonthermal irreversible electroporation with 3000 V/cm can be used for thyroid ablation. Possible applications are treatment of hyperthyroidism and thyroid cancer. The highly heterogeneous structure of the thyroid distorts the electric fields and temperature distribution in the thyroid must be considered when designing treatment protocols for this tissue type.

scholarly journals Numerical simulation modeling of the irreversible electroporation treatment zone for focal therapy of prostate cancer, correlation with whole-mount pathology and T2-weighted MRI sequences

2019 ◽  
Vol 11 ◽  
pp. 175628721985230 ◽  
Author(s):  
Matthijs J. Scheltema ◽  
Tim J. O’Brien ◽  
Willemien van den Bos ◽  
Daniel M. de Bruin ◽  
Rafael V. Davalos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Irreversible Electroporation ◽  
Prostate Tissue ◽  
Human Prostate ◽  
Ablation Zone ◽  
Electrical Field ◽  
Whole Mount ◽  
Human Prostate Tissue ◽  
Mri Sequences

Background: At present, it is not possible to predict the ablation zone volume following irreversible electroporation (IRE) for prostate cancer (PCa). This study aimed to determine the necessary electrical field threshold to ablate human prostate tissue in vivo with IRE. Methods: In this prospective multicenter trial, patients with localized PCa were treated with IRE 4 weeks before their scheduled radical prostatectomy. In 13 patients, numerical models of the electrical field were generated and compared with the ablation zone volume on whole-mount pathology and T2-weighted magnetic resonance imaging (MRI) sequences. Volume-generating software was used to calculate the ablation zone volumes on histology and MRI. The electric field threshold to ablate prostate tissue was determined for each patient. Results: A total of 13 patients were included for histological and simulation analysis. The median electrical field threshold was 550 V/cm (interquartile range 383–750 V/cm) for the software-generated histology volumes. The median electrical field threshold was 500 V/cm (interquartile range 386–580 V/cm) when the ablation zone volumes were used from the follow-up MRI. Conclusions: The electrical field threshold to ablate human prostate tissue in vivo was determined using whole-mount pathology and MRI. These thresholds may be used to develop treatment planning or monitoring software for IRE prostate ablation; however, further optimization of simulation methods are required to decrease the variance that was observed between patients.

scholarly journals Careful treatment planning enables safe ablation of liver tumors adjacent to major blood vessels by percutaneous irreversible electroporation (IRE)

2015 ◽  
Vol 49 (3) ◽  
pp. 234-241 ◽  
Author(s):  
Bor Kos ◽  
Peter Voigt ◽  
Damijan Miklavcic ◽  
Michael Moche
Keyword(s):  
Electric Field ◽  
Blood Vessels ◽  
Treatment Planning ◽  
Hepatic Vein ◽  
Thermal Ablation ◽  
Pulse Generator ◽  
Liver Tumors ◽  
Irreversible Electroporation ◽  
Distance Ratio ◽  
Contrast Enhanced Ct

AbstractBackground.Irreversible electroporation (IRE) is a tissue ablation method, which relies on the phenomenon of electroporation. When cells are exposed to a sufficiently electric field, the plasma membrane is disrupted and cells undergo an apoptotic or necrotic cell death. Although heating effects are known IRE is considered as non-thermal ablation technique and is currently applied to treat tumors in locations where thermal ablation techniques are contraindicated.Materials and methods.The manufacturer of the only commercially available pulse generator for IRE recommends a voltage-to-distance ratio of 1500 to 1700 V/cm for treating tumors in the liver. However, major blood vessels can influence the electric field distribution. We present a method for treatment planning of IRE which takes the influence of blood vessels on the electric field into account; this is illustrated on a treatment of 48-year-old patient with a metastasis near the remaining hepatic vein after a right side hemi-hepatectomy.Results.Output of the numerical treatment planning method shows that a 19.9 cm3irreversible electroporation lesion was generated and the whole tumor was covered with at least 900 V/cm. This compares well with the volume of the hypodense lesion seen in contrast enhanced CT images taken after the IRE treatment. A significant temperature raise occurs near the electrodes. However, the hepatic vein remains open after the treatment without evidence of tumor recurrence after 6 months.Conclusions.Treatment planning using accurate computer models was recognized as important for electrochemotherapy and irreversible electroporation. An important finding of this study was, that the surface of the electrodes heat up significantly. Therefore the clinical user should generally avoid placing the electrodes less than 4 mm away from risk structures when following recommendations of the manufacturer.

The Effects of Large Blood Vessels on Three-Dimensional Tissue Temperature Distributions During Electromagnetic Induced Nano-Hyperthermia: Numerical Simulation

2008 ◽  
Author(s):  
Zhong-Shan Deng ◽  
Jing Liu
Keyword(s):  
Blood Vessels ◽  
Tumor Cells ◽  
Three Dimensional ◽  
The Body ◽  
Thermal Therapy ◽  
Tissue Temperature ◽  
Surrounding Tissue ◽  
Temperature Profiles ◽  
Hyperthermia Treatment ◽  
Tumor Hyperthermia

As is well known, the blood flowing through large blood vessels acts as a heat sink and plays an important role in affecting temperature profiles of heated tissues [1]. In hyperthermia, heating is usually limited to the tumor and a small margin of the surrounding tissue. Since the temperatures in the rest of the body remain normal, the blood that supplies the tumor will be relatively cold. Consequently, the blood flow inside a large vessel will represent a sink which cools the nearby heated tissues and then limits heating lesion during tumor hyperthermia. Under this adverse condition, a part of vital tumor cells may remain in the thermally lethal area and lead to recurrence of tumors after hyperthermia treatment. More specifically, tumor cell survival in the vicinity of large blood vessels is often correlated with tumor recurrence after thermal therapy. Therefore, it is difficult to implement an effective hyperthermia treatment when a tumor is contiguous to a large blood vessel or such vessel transits the tumor. How to totally destroy tumor cells in the vicinity of large blood vessels has been a major challenge in hyperthermia [2].

scholarly journals The Effect of Irreversible Electroporation on Blood Vessels

2007 ◽  
Vol 6 (4) ◽  
pp. 307-312 ◽  
Author(s):  
Elad Maor ◽  
Antoni Ivorra ◽  
Jonathan Leor ◽  
Boris Rubinsky
Keyword(s):  
Smooth Muscle ◽  
Pilot Study ◽  
Blood Vessels ◽  
Arterial Wall ◽  
Thrombus Formation ◽  
Irreversible Electroporation ◽  
Long Term Effects ◽  
Tissue Conductivity ◽  
Matrix Components

We present a pilot study on the long term effects of irreversible electroporation (IRE) on a large blood vessel. The study was motivated by the anticipated use of IRE for treatment of cancer tumors abutting large blood vessels. A sequence of 10 direct current IRE pulses of 3800 V/cm, 100μs each, at a frequency of 10 pulses per second, were applied directly to the carotid artery in six rats. Measuring tissue conductivity during the procedure showed, as predicted, an increase in conductivity during the application of the pulse, which suggests that this measurement can be used to control the application of IRE. All the animals survived the procedure and showed no side effects. Histology performed 28 days after the procedure showed that the connective matrix of the blood vessels remained intact and the number of vascular smooth muscle cells (VSMC) in the arterial wall decreased with no evidence of aneurysm, thrombus formation or necrosis. Average VSMC density was significantly lower following IRE ablation compared with control (24 ± 11 vs. 139 ± 14, P<0.001), with no apparent damage to extra cellular matrix components and structure. In addition to the relevance of this study to treatment of cancer near large blood vessels these findings tentatively suggest that IRE has possible applications to treatment of pathological processes in which it is desired to reduce the proliferation of VSMC population, such as restenosis and for attenuating atherosclerotic processes in clinical important locations such as coronary, carotid and renal arteries.

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